Yang Xiao-Ming, Wang Yun-Fei, Li Yue-Ying, Ma Hai-Le
School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China.
School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China.
Fitoterapia. 2014 Oct;98:66-76. doi: 10.1016/j.fitote.2014.07.003. Epub 2014 Jul 10.
Ginkgolic acids are alkylsalicylic acid derivatives with a thermolabile carboxylic group from Ginkgo biloba L., and they exhibit anticancer activity. Their anticancer effects are closely associated with their thermal stability. In this study, the thermal decomposition of ginkgolic acids was analyzed at temperatures of 30, 50, 70 and 250°C. The results clearly showed that an obvious slow decarboxylation of the ginkgolic acids was detected at 70°C. When the temperature increased to 250°C, the decarboxylation reaction was rapidly completed. The ginkgolic acids were decarboxylated to yield ginkgols. The ginkgols C13:0, C15:1 and C17:1 were separated and definitively identified by IR, NMR and GC-MS. The cytotoxic effects of ginkgols C13:0, C15:1 and C17:1 were tested and compared with those of the corresponding ginkgolic acids. An MTT assay showed that ginkgol C17:1 (48-h IC50=8.5 μg·ml(-1)) has the strongest inhibition on SMMC-7721 cells in a dose- and time-dependent manner. The anticancer action may occur via the induction of apoptosis by the activation of caspases-3, the upregulation of Bax expression, and the inhibition migration of SMMC7721 cells. The results indicated that ginkgol C17:1 might be useful for the further development of a hepatocellular carcinoma preventive agent.
银杏酸是来自银杏叶的具有热不稳定羧基的烷基水杨酸衍生物，它们具有抗癌活性。它们的抗癌作用与其热稳定性密切相关。在本研究中，分析了银杏酸在30、50、70和250℃温度下的热分解情况。结果清楚地表明，在70℃时检测到银杏酸明显的缓慢脱羧反应。当温度升至250℃时，脱羧反应迅速完成。银杏酸脱羧生成银杏酚。通过红外光谱、核磁共振和气相色谱-质谱联用对银杏酚C13:0、C15:1和C17:1进行了分离和确证鉴定。测试了银杏酚C13:0、C15:1和C17:1的细胞毒性作用，并与相应的银杏酸进行了比较。MTT法显示，银杏酚C17:1（48小时半数抑制浓度=8.5μg·ml(-1)）对SMMC-7721细胞具有最强的抑制作用，呈剂量和时间依赖性。抗癌作用可能通过激活半胱天冬酶-3诱导细胞凋亡、上调Bax表达以及抑制SMMC7721细胞迁移而发生。结果表明，银杏酚C17:1可能有助于进一步开发肝细胞癌预防剂。
